SIDS.Words
--Common cardiac gene linked to sudden infant death in African Americans--
(Shorter version appearing on ScienceNOW, Wednesday, February 1)
Infants with 2 copies of a common variant in a gene associated with irregular heartbeat are 24 times more likely to experience sudden death, a new study shows.
The variant, considered common because it is present in over 10% of African Americans, does not cause sudden infant death syndrome (SIDS) on its own, nor is it a problem when present in one copy. However, a double dose of the defect seems to make infants more vulnerable to environmental stresses that are typically associated with SIDS and that healthy children can easily tolerate.
"The common polymorphism alone does not cause SIDS," said Steven Goldstein, M.D., Ph.D., professor and chairman of pediatrics at the University of Chicago and director of the study. "Our findings suggest, however, that it renders infants vulnerable to environmental challenges -- such as a long pause in respiration -- that are tolerated by children without the mutation."
"The hope," he added, "is that findings like this may one day allow us to intervene. We might screen to identify children at high risk and teach parents how to lessen the likelihood of secondary challenges. We have already begun to evaluate drugs that may mitigate the risk."
SIDS is the sudden and unexpected death of a child with no detectable lethal disorder. It is the leading cause of infant mortality in the United States among infants between one month and one year of age. While research suggests that environmental factors – like sleeping on the stomach or exposure to second-hand smoke – are partly to blame, the fact that African Americans are three times more likely than Caucasians, and six times more likely than Hispanics or Asians to experience sudden death, suggests an important role for genetics, too.
Particular genetic variation tends to run in ethnic groups. Yet no previous work has specifcally examined a group of African American SIDS victims to understand how genetic variation might contribute to SIDS in this cohort. “That’s what is different about this study,” said Alfred George, M.D., chief of the Division of Genetic Medicine at Vanderbilt University School of Medicine.
Goldstein and colleagues at the University of Chicago studied genes in the heart tissue of 133 African American infants diagnosed, after autopsy, with SIDS. Goldstein’s search focused on abnormalities in one gene in particular: SCN5A, which codes for a sodium ion channel in the heart and in which rare SIDS-related mutations had previously been found. His team indentified genetic variants in SCN5A, observing that one variant in particular, Y1103, was 24 times more frequent in two alleles in SIDS victims than it was in healthy individuals. Goldstein had no idea how a double dose of Y1103 increased risk of SIDS, however, since it did not appear to hinder ion channel operation – or interrupt heartbeat -- under normal conditions.
SIDS is not purely genetic, though, and Goldstein decided to consider environmental triggers, too. It is known that sudden death occurs in settings of interrupted breathing, common in infants who sleep on their stomachs. Interrupted breathing deprives cells of oxygen and causes a slight increase in acid levels in the blood.
Goldstein simulated this acidic environment in culture, and then compared cells with the Y1103 mutation against normal cells. The cells with the abnormal channels misbehaved in acidic conditions; they could not regulate sodium ion levels, a difficulty which leads to changes known to increase the risk for abnormal heart rhythms and sudden death. The Chicago team speculates online February in the Journal of Clinical Investigation that, in the setting of impaired breathing, SIDS occurs more readily when an individual carries two copies of Y1103.
“This study doesn’t imply that Y1103 is the only genetic factor in SIDS,” George explained. “However, it supports the idea that genetic variation coupled with a specific environmental stressor, like acidosis, may trigger sudden death. The study emphasizes the need to determine the true incidence of genetic causes of sudden death in infants. Once that’s done, a decision can be made as to the rationale and cost effectiveness of general population screening for these genetic factors.”
According to Debra E. Weese-Mayer, M.D, professor of pediatrics at Rush University's Center for SIDS Research in Chicago, “the study is a major step forward in terms of the sophisticated kind of analsyis that should be expected as additional cardiac rhythm genes are considered in SIDS.”
.MGW.
(Shorter version appearing on ScienceNOW, Wednesday, February 1)
Infants with 2 copies of a common variant in a gene associated with irregular heartbeat are 24 times more likely to experience sudden death, a new study shows.
The variant, considered common because it is present in over 10% of African Americans, does not cause sudden infant death syndrome (SIDS) on its own, nor is it a problem when present in one copy. However, a double dose of the defect seems to make infants more vulnerable to environmental stresses that are typically associated with SIDS and that healthy children can easily tolerate.
"The common polymorphism alone does not cause SIDS," said Steven Goldstein, M.D., Ph.D., professor and chairman of pediatrics at the University of Chicago and director of the study. "Our findings suggest, however, that it renders infants vulnerable to environmental challenges -- such as a long pause in respiration -- that are tolerated by children without the mutation."
"The hope," he added, "is that findings like this may one day allow us to intervene. We might screen to identify children at high risk and teach parents how to lessen the likelihood of secondary challenges. We have already begun to evaluate drugs that may mitigate the risk."
SIDS is the sudden and unexpected death of a child with no detectable lethal disorder. It is the leading cause of infant mortality in the United States among infants between one month and one year of age. While research suggests that environmental factors – like sleeping on the stomach or exposure to second-hand smoke – are partly to blame, the fact that African Americans are three times more likely than Caucasians, and six times more likely than Hispanics or Asians to experience sudden death, suggests an important role for genetics, too.
Particular genetic variation tends to run in ethnic groups. Yet no previous work has specifcally examined a group of African American SIDS victims to understand how genetic variation might contribute to SIDS in this cohort. “That’s what is different about this study,” said Alfred George, M.D., chief of the Division of Genetic Medicine at Vanderbilt University School of Medicine.
Goldstein and colleagues at the University of Chicago studied genes in the heart tissue of 133 African American infants diagnosed, after autopsy, with SIDS. Goldstein’s search focused on abnormalities in one gene in particular: SCN5A, which codes for a sodium ion channel in the heart and in which rare SIDS-related mutations had previously been found. His team indentified genetic variants in SCN5A, observing that one variant in particular, Y1103, was 24 times more frequent in two alleles in SIDS victims than it was in healthy individuals. Goldstein had no idea how a double dose of Y1103 increased risk of SIDS, however, since it did not appear to hinder ion channel operation – or interrupt heartbeat -- under normal conditions.
SIDS is not purely genetic, though, and Goldstein decided to consider environmental triggers, too. It is known that sudden death occurs in settings of interrupted breathing, common in infants who sleep on their stomachs. Interrupted breathing deprives cells of oxygen and causes a slight increase in acid levels in the blood.
Goldstein simulated this acidic environment in culture, and then compared cells with the Y1103 mutation against normal cells. The cells with the abnormal channels misbehaved in acidic conditions; they could not regulate sodium ion levels, a difficulty which leads to changes known to increase the risk for abnormal heart rhythms and sudden death. The Chicago team speculates online February in the Journal of Clinical Investigation that, in the setting of impaired breathing, SIDS occurs more readily when an individual carries two copies of Y1103.
“This study doesn’t imply that Y1103 is the only genetic factor in SIDS,” George explained. “However, it supports the idea that genetic variation coupled with a specific environmental stressor, like acidosis, may trigger sudden death. The study emphasizes the need to determine the true incidence of genetic causes of sudden death in infants. Once that’s done, a decision can be made as to the rationale and cost effectiveness of general population screening for these genetic factors.”
According to Debra E. Weese-Mayer, M.D, professor of pediatrics at Rush University's Center for SIDS Research in Chicago, “the study is a major step forward in terms of the sophisticated kind of analsyis that should be expected as additional cardiac rhythm genes are considered in SIDS.”
.MGW.
posted by Meagan G at
10:21 AM
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